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PDBsum entry 2asj

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protein dna_rna metals links
Transferase/DNA PDB id
2asj
Jmol
Contents
Protein chains
341 a.a. *
DNA/RNA
Metals
_CA ×3
Waters ×144
* Residue conservation analysis
PDB id:
2asj
Name: Transferase/DNA
Title: Oxog-modified preinsertion binary complex
Structure: 5'-d( Gp Gp Tp Tp Gp Gp Ap Tp Gp Gp Tp Ap (Ddg))- chain: d, h. Engineered: yes. Other_details: primer strand (dideoxy-terminated at 3'-end) 5'-d( Cp Tp Ap Ap Cp (8Og) Cp Tp Ap Cp Cp Ap Tp Cp Cp Ap Ap Cp C)-3'. Chain: e, j. Engineered: yes. Other_details: oxog-modified template strand.
Source: Synthetic: yes. Sulfolobus solfataricus. Organism_taxid: 2287. Gene: dbh, dpo4. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Trimer (from PQS)
Resolution:
2.35Å     R-factor:   0.249     R-free:   0.318
Authors: O.Rechkoblit,L.Malinina,Y.Cheng,V.Kuryavyi,S.Broyde,N.E.Geac D.J.Patel
Key ref: O.Rechkoblit et al. (2006). Stepwise translocation of Dpo4 polymerase during error-free bypass of an oxoG lesion. PLoS Biol, 4, e11-18. PubMed id: 16379496
Date:
23-Aug-05     Release date:   10-Jan-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q97W02  (DPO4_SULSO) -  DNA polymerase IV
Seq:
Struc:
352 a.a.
341 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.2.7.7.7  - DNA-directed Dna polymerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
Deoxynucleoside triphosphate
+ DNA(n)
= diphosphate
+ DNA(n+1)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     response to DNA damage stimulus   4 terms 
  Biochemical function     transferase activity     7 terms  

 

 
    reference    
 
 
PLoS Biol 4:e11-18 (2006)
PubMed id: 16379496  
 
 
Stepwise translocation of Dpo4 polymerase during error-free bypass of an oxoG lesion.
O.Rechkoblit, L.Malinina, Y.Cheng, V.Kuryavyi, S.Broyde, N.E.Geacintov, D.J.Patel.
 
  ABSTRACT  
 
7,8-dihydro-8-oxoguanine (oxoG), the predominant lesion formed following oxidative damage of DNA by reactive oxygen species, is processed differently by replicative and bypass polymerases. Our kinetic primer extension studies demonstrate that the bypass polymerase Dpo4 preferentially inserts C opposite oxoG, and also preferentially extends from the oxoG*C base pair, thus achieving error-free bypass of this lesion. We have determined the crystal structures of preinsertion binary, insertion ternary, and postinsertion binary complexes of oxoG-modified template-primer DNA and Dpo4. These structures provide insights into the translocation mechanics of the bypass polymerase during a complete cycle of nucleotide incorporation. Specifically, during noncovalent dCTP insertion opposite oxoG (or G), the little-finger domain-DNA phosphate contacts translocate by one nucleotide step, while the thumb domain-DNA phosphate contacts remain fixed. By contrast, during the nucleotidyl transfer reaction that covalently incorporates C opposite oxoG, the thumb-domain-phosphate contacts are translocated by one nucleotide step, while the little-finger contacts with phosphate groups remain fixed. These stepwise conformational transitions accompanying nucleoside triphosphate binding and covalent nucleobase incorporation during a full replication cycle of Dpo4-catalyzed bypass of the oxoG lesion are distinct from the translocation events in replicative polymerases.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21300901 K.N.Kirouac, and H.Ling (2011).
Unique active site promotes error-free replication opposite an 8-oxo-guanine lesion by human DNA polymerase iota.
  Proc Natl Acad Sci U S A, 108, 3210-3215.
PDB codes: 3q8p 3q8q 3q8r
21354175 R.Vasquez-Del Carpio, T.D.Silverstein, S.Lone, R.E.Johnson, L.Prakash, S.Prakash, and A.K.Aggarwal (2011).
Role of human DNA polymerase κ in extension opposite from a cis-syn thymine dimer.
  J Mol Biol, 408, 252-261.
PDB code: 3pzp
20846959 S.M.Sherrer, K.A.Fiala, J.D.Fowler, S.A.Newmister, J.M.Pryor, and Z.Suo (2011).
Quantitative analysis of the efficiency and mutagenic spectra of abasic lesion bypass catalyzed by human Y-family DNA polymerases.
  Nucleic Acids Res, 39, 609-622.  
20582735 D.Ma, J.D.Fowler, C.Yuan, and Z.Suo (2010).
Backbone assignment of the catalytic core of a Y-family DNA polymerase.
  Biomol NMR Assign, 4, 207-209.  
19969000 H.Zhang, and F.P.Guengerich (2010).
Effect of N2-guanyl modifications on early steps in catalysis of polymerization by Sulfolobus solfataricus P2 DNA polymerase Dpo4 T239W.
  J Mol Biol, 395, 1007-1018.  
20123134 J.D.Pata (2010).
Structural diversity of the Y-family DNA polymerases.
  Biochim Biophys Acta, 1804, 1124-1135.  
19942858 J.Lu, and Y.Liu (2010).
Deletion of Ogg1 DNA glycosylase results in telomere base damage and length alteration in yeast.
  EMBO J, 29, 398-409.  
20154704 O.Rechkoblit, A.Kolbanovskiy, L.Malinina, N.E.Geacintov, S.Broyde, and D.J.Patel (2010).
Mechanism of error-free and semitargeted mutagenic bypass of an aromatic amine lesion by Y-family polymerase Dpo4.
  Nat Struct Mol Biol, 17, 379-388.
PDB codes: 3khg 3khh 3khl 3khr
20400942 S.Obeid, N.Blatter, R.Kranaster, A.Schnur, K.Diederichs, W.Welte, and A.Marx (2010).
Replication through an abasic DNA lesion: structural basis for adenine selectivity.
  EMBO J, 29, 1738-1747.
PDB codes: 3lwl 3lwm
21070945 T.D.Silverstein, R.Jain, R.E.Johnson, L.Prakash, S.Prakash, and A.K.Aggarwal (2010).
Structural basis for error-free replication of oxidatively damaged DNA by yeast DNA polymerase η.
  Structure, 18, 1463-1470.
PDB codes: 3oha 3ohb
20526335 V.K.Batra, W.A.Beard, E.W.Hou, L.C.Pedersen, R.Prasad, and S.H.Wilson (2010).
Mutagenic conformation of 8-oxo-7,8-dihydro-2'-dGTP in the confines of a DNA polymerase active site.
  Nat Struct Mol Biol, 17, 889-890.
PDB code: 3mby
19542228 A.Irimia, R.L.Eoff, F.P.Guengerich, and M.Egli (2009).
Structural and functional elucidation of the mechanism promoting error-prone synthesis by human DNA polymerase kappa opposite the 7,8-dihydro-8-oxo-2'-deoxyguanosine adduct.
  J Biol Chem, 284, 22467-22480.
PDB codes: 2w7o 2w7p
19758983 G.E.Damsma, and P.Cramer (2009).
Molecular basis of transcriptional mutagenesis at 8-oxoguanine.
  J Biol Chem, 284, 31658-31663.
PDB codes: 3i4m 3i4n
19837980 H.Zhang, J.W.Beckman, and F.P.Guengerich (2009).
Frameshift deletion by Sulfolobus solfataricus P2 DNA polymerase Dpo4 T239W is selective for purines and involves normal conformational change followed by slow phosphodiester bond formation.
  J Biol Chem, 284, 35144-35153.  
19059910 H.Zhang, R.L.Eoff, I.D.Kozekov, C.J.Rizzo, M.Egli, and F.P.Guengerich (2009).
Versatility of Y-family Sulfolobus solfataricus DNA Polymerase Dpo4 in Translesion Synthesis Past Bulky N2-Alkylguanine Adducts.
  J Biol Chem, 284, 3563-3576.
PDB codes: 2v4s 2v4t 2w8k 2w8l
19542237 H.Zhang, R.L.Eoff, I.D.Kozekov, C.J.Rizzo, M.Egli, and F.P.Guengerich (2009).
Structure-function relationships in miscoding by Sulfolobus solfataricus DNA polymerase Dpo4: guanine N2,N2-dimethyl substitution produces inactive and miscoding polymerase complexes.
  J Biol Chem, 284, 17687-17699.
PDB codes: 2w9a 2w9b 2w9c
19446518 J.J.Perry, K.Hitomi, and J.A.Tainer (2009).
Flexibility promotes fidelity.
  Structure, 17, 633-634.  
19464298 M.K.Swan, R.E.Johnson, L.Prakash, S.Prakash, and A.K.Aggarwal (2009).
Structure of the human Rev1-DNA-dNTP ternary complex.
  J Mol Biol, 390, 699-709.
PDB code: 3gqc
19446528 O.Rechkoblit, L.Malinina, Y.Cheng, N.E.Geacintov, S.Broyde, and D.J.Patel (2009).
Impact of conformational heterogeneity of OxoG lesions and their pairing partners on bypass fidelity by Y family polymerases.
  Structure, 17, 725-736.
PDB codes: 3gii 3gij 3gik 3gil 3gim
19515847 R.L.Eoff, R.Sanchez-Ponce, and F.P.Guengerich (2009).
Conformational Changes during Nucleotide Selection by Sulfolobus solfataricus DNA Polymerase Dpo4.
  J Biol Chem, 284, 21090-21099.  
19492058 R.Vasquez-Del Carpio, T.D.Silverstein, S.Lone, M.K.Swan, J.R.Choudhury, R.E.Johnson, S.Prakash, L.Prakash, and A.K.Aggarwal (2009).
Structure of human DNA polymerase kappa inserting dATP opposite an 8-OxoG DNA lesion.
  PLoS One, 4, e5766.
PDB codes: 3hed 3in5
19282446 S.D.McCulloch, R.J.Kokoska, P.Garg, P.M.Burgers, and T.A.Kunkel (2009).
The efficiency and fidelity of 8-oxo-guanine bypass by DNA polymerases delta and eta.
  Nucleic Acids Res, 37, 2830-2840.  
19124465 S.M.Sherrer, J.A.Brown, L.R.Pack, V.P.Jasti, J.D.Fowler, A.K.Basu, and Z.Suo (2009).
Mechanistic Studies of the Bypass of a Bulky Single-base Lesion Catalyzed by a Y-family DNA Polymerase.
  J Biol Chem, 284, 6379-6388.  
19200715 S.Schneider, S.Schorr, and T.Carell (2009).
Crystal structure analysis of DNA lesion repair and tolerance mechanisms.
  Curr Opin Struct Biol, 19, 87-95.  
19354292 V.Vooradi, and L.J.Romano (2009).
Effect of N-2-acetylaminofluorene and 2-aminofluorene adducts on DNA binding and synthesis by yeast DNA polymerase eta.
  Biochemistry, 48, 4209-4216.  
18689842 D.Dalevi, N.N.Ivanova, K.Mavromatis, S.D.Hooper, E.Szeto, P.Hugenholtz, N.C.Kyrpides, and V.M.Markowitz (2008).
Annotation of metagenome short reads using proxygenes.
  Bioinformatics, 24, i7-13.  
18984592 J.W.Beckman, Q.Wang, and F.P.Guengerich (2008).
Kinetic Analysis of Correct Nucleotide Insertion by a Y-family DNA Polymerase Reveals Conformational Changes Both Prior to and following Phosphodiester Bond Formation as Detected by Tryptophan Fluorescence.
  J Biol Chem, 283, 36711-36723.  
18407502 S.Broyde, L.Wang, O.Rechkoblit, N.E.Geacintov, and D.J.Patel (2008).
Lesion processing: high-fidelity versus lesion-bypass DNA polymerases.
  Trends Biochem Sci, 33, 209-219.  
17375926 L.Wang, X.Yu, P.Hu, S.Broyde, and Y.Zhang (2007).
A water-mediated and substrate-assisted catalytic mechanism for Sulfolobus solfataricus DNA polymerase IV.
  J Am Chem Soc, 129, 4731-4737.  
17550419 M.V.García-Ortiz, T.Roldán-Arjona, and R.R.Ariza (2007).
The noncatalytic C-terminus of AtPOLK Y-family DNA polymerase affects synthesis fidelity, mismatch extension and translesion replication.
  FEBS J, 274, 3340-3350.  
17652324 M.de Vega, and M.Salas (2007).
A highly conserved Tyrosine residue of family B DNA polymerases contributes to dictate translesion synthesis past 8-oxo-7,8-dihydro-2'-deoxyguanosine.
  Nucleic Acids Res, 35, 5096-5107.  
17090533 R.A.Perlow-Poehnelt, I.Likhterov, L.Wang, D.A.Scicchitano, N.E.Geacintov, and S.Broyde (2007).
Increased flexibility enhances misincorporation: temperature effects on nucleotide incorporation opposite a bulky carcinogen-DNA adduct by a Y-family DNA polymerase.
  J Biol Chem, 282, 1397-1408.  
17468100 R.L.Eoff, A.Irimia, K.C.Angel, M.Egli, and F.P.Guengerich (2007).
Hydrogen bonding of 7,8-dihydro-8-oxodeoxyguanosine with a charged residue in the little finger domain determines miscoding events in Sulfolobus solfataricus DNA polymerase Dpo4.
  J Biol Chem, 282, 19831-19843.
PDB codes: 2uvr 2uvu 2uvv 2uvw
17898175 W.Yang, and R.Woodgate (2007).
What a difference a decade makes: insights into translesion DNA synthesis.
  Proc Natl Acad Sci U S A, 104, 15591-15598.  
16452300 L.Wang, and S.Broyde (2006).
A new anti conformation for N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (AAF-dG) allows Watson-Crick pairing in the Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4).
  Nucleic Acids Res, 34, 785-795.  
16820532 L.Zhang, O.Rechkoblit, L.Wang, D.J.Patel, R.Shapiro, and S.Broyde (2006).
Mutagenic nucleotide incorporation and hindered translocation by a food carcinogen C8-dG adduct in Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4): modeling and dynamics studies.
  Nucleic Acids Res, 34, 3326-3337.  
16679449 M.A.Kalam, K.Haraguchi, S.Chandani, E.L.Loechler, M.Moriya, M.M.Greenberg, and A.K.Basu (2006).
Genetic effects of oxidative DNA damages: comparative mutagenesis of the imidazole ring-opened formamidopyrimidines (Fapy lesions) and 8-oxo-purines in simian kidney cells.
  Nucleic Acids Res, 34, 2305-2315.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.